探花合集

This Week in the 探花合集 Weekly

The field of addiction is continuously in search of a unifying language—a balance between words, terms, and even stigma. But a seemingly intuitive concept can sometimes become an obstacle if it’s difficult to define. Such is the case with treatment-refractory addiction (TRA), a concept in search of a definition that has been the focus of three commentaries (, , ), an ASAM Weekly , and now, a scoping review ().

Although definitions of TRA vary widely, three important themes have emerged: severity of use, treatment response, and psychosocial impairment. Severity of use happens to be a well-accepted concept whether it's applied to the opioid crisis () or high-potency cannabis (). Treatment response is understandably more open to debate, for example, when it’s not clear if the individual or the treatment “failed” (). On the other hand, psychosocial impairments should really be an end point we can all agree on, but social determinants of health show us how biased end points can be ().

Treatment-resistant depression (TRD) is often used as an example to help define TRA. But if we consider all of addiction’s diversities—from substances like benzodiazepines () and nicotine () to behavioral addictions like gambling () and problematic pornography use ()—it becomes evident that we need an example for TRA that is more unifying than TRD. We would need something equivalent to treatment-resistant mental illness, but that also is not well-defined. 

So rather than define treatment-refractory for all addictions, we should probably pick one addiction and start from there. At that point, TRD would be the intuitive example that helps us define a first of many treatment-refractory addictions.

Thanks for reading,

Nicholas Athanasiou, MD, MBA, DFASAM
Editor in Chief

with Co-Editors: Brandon Aden, MD, MPH, FASAM; John A. Fromson, MD; Jack Woodside, MD

Lead Story 

Journal of Addiction Medicine

This scoping review examined inconsistent terminology that is used in addiction research to describe individuals undergoing multiple treatments without a remission. Researchers found that “treatment-resistant” and “treatment-refractory” were the most commonly used terms, often in alcohol and opioid studies. The most comprehensive definitions incorporated thresholds for amount/frequency consumed, duration of addiction or age of onset, number of treatment encounters, treatment duration, and a pharmacological treatment trial. The use of “treatment-refractory” over “treatment-resistant” may better align with person-first language, emphasizing the multifaceted nature of addiction rather than implying something about the individual. An agreed-upon definition may also improve the identification of this resource-intensive and at-risk population, guiding the development of tailored interventions that better address their treatment needs.

Research and Science 

Journal of the American Medical Association

This cohort study of 4,285 US adolescents assessed if addictive screen use trajectories were associated with suicidal behaviors, suicidal ideation, and mental health outcomes in US youth. Adolescents in the study showed increasing addictive use trajectories for social media (31.3%) and mobile phones (24.6%) over 4 years. High or increasing addictive use trajectories were associated with elevated risks of suicidal behaviors or ideation compared with low addictive use. Youths with high-peaking or increasing social media use or high video game use had more internalizing or externalizing symptoms. Both high and increasing addictive screen use trajectories were associated with suicidal behaviors, suicidal ideation, and worse mental health in youths.

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BMJ

As part of the BMJ Rapid Recommendations project the authors conducted a systematic review, including 58 studies, to evaluate the evidence for strategies to deprescribe benzodiazepines and sedative hypnotics (BSH). Overall, they found low-certainty evidence that patient education, mediation reviews, and pharmacist-led educational interventions may increase the proportion of patients who stop BSH use. In addition, the authors found very low to no certainty for effects for multiple other interventions, including education of physicians, cognitive behavioral therapy, and drug-assisted tapering. There was low-certainty evidence that multicomponent interventions were more effective than single-component interventions. The authors note the need for additional research given these findings. 

Nature Metabolism

This highly technical and complex article describes a series of experiments in mice that investigate the mechanisms that glucagon-like peptide-1 (GLP-1) uses to regulate appetite, feeding, and energy homeostasis. GLP-1 activates neurons in the hypothalamus (lateral hypothalamus and paraventricular hypothalamus). These areas in the hypothalamus regulate food intake, and destroying them leads to hyperphagia and obesity. There are also 2 regions in the brainstem known to regulate food intake. This study reveals a neural pathway connecting these regions in the hypothalamus and brainstem that is important in GLP-1 control of feeding. Blocking this pathway results in hyperphagia and obesity. When hunger is induced by low energy levels this pathway is suppressed. Better understanding of these mechanisms will allow more effective clinical interventions.

Drug and Alcohol Dependence

For this study, researchers collected 260 drug samples between March 2024 and March 2025 at a harm reduction center in Philadelphia. The compounds in the samples were analyzed by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Fentanyl was detected in 98% and xylazine was detected in 65% of samples. Over time fentanyl concentration dropped from 9.6% to 5.3%. Xylazine prevalence dropped from 100% to 58% of samples. Lidocaine and tetracaine prevalence increased from 3% to 63% of samples. Two new compounds appeared — medetomidine (a veterinary analgesic) and BTMPS (used in plastics manufacturing). By March 2025 these reached prevalences of 83% and 25% of samples, respectively. The composition of the street opioid supply is rapidly changing, and improved systems for drug checking are needed to inform health providers and improve patient care.

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JHEP Reports

The alcohol-harm paradox refers to the phenomenon that patients from lower socioeconomic groups suffer more alcohol-related illness despite drinking the same or even lower amounts of alcohol than affluent patients. However, prior to 1980 alcohol-related mortality was proportional to the amount of alcohol consumed and not related to social class. The authors note that lower socioeconomic groups are more likely to binge drink which has greater effects on the liver than gradual consumption of alcohol. Metabolic risk factors (obesity, diabetes, hyperlipidemia) contributing to liver disease are more common in lower socioeconomic groups, and over 65% of patients considered to have non-alcoholic cirrhosis in fact have heavy alcohol use. Other factors of the alcohol-harm paradox include poor access to health care, liver transplant, more alcohol outlets in poor communities, and drinking to cope with the trauma of economic deprivation.

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Addiction 

As on-line gambling has increased significantly in the last several years, there are questions about how design features could influence gambling harms. It is known that structural characteristics of physical gambling establishments can influence gambling behaviors, but evaluation of on-line gambling platforms has not occurred in the same way. In addition, these digital platforms can quickly adapt, add new features, and allow gambling operators to quickly assess the impact of changes on user behavior. The authors state, given this growth and adaptability, there is a need for regulators to anticipate forthcoming technologies and potential negative consequences.

Pediatric Research

This mini review is a conceptual overview of evidence from preclinical and clinical studies, providing understanding of how prenatal cannabis use impacts maternal physiology and fetal development across multiple organ systems. Prenatal cannabis exposure disrupts maternal metabolic regulation, placental function, and fetal development, leading to adverse short- and long-term outcomes. Emerging data reveal that even early or brief cannabis exposure during pregnancy is associated with fetal growth restriction, altered neurodevelopmental trajectories, and increased long-term risk for obesity, diabetes, and cardiovascular disease.

In the News 

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STAT

The Washington Post

The Wall Street Journal

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The Palm Beach Post

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MassLive

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The Charlotte Observer

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PsyPost